Effect of asymmetric dimethylarginine (ADMA) on heart failure development

Nitric Oxide. 2016 Apr 1:54:73-81. doi: 10.1016/j.niox.2016.02.006. Epub 2016 Feb 24.

Abstract

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases that limits nitric oxide bioavailability and can increase production of NOS derived reactive oxidative species. Increased plasma ADMA is a one of the strongest predictors of mortality in patients who have had a myocardial infarction or suffer from chronic left heart failure, and is also an independent risk factor for several other conditions that contribute to heart failure development, including hypertension, coronary artery disease/atherosclerosis, diabetes, and renal dysfunction. The enzyme responsible for ADMA degradation is dimethylarginine dimethylaminohydrolase-1 (DDAH1). DDAH1 plays an important role in maintaining nitric oxide bioavailability and preserving cardiovascular function in the failing heart. Here, we examine mechanisms of abnormal NO production in heart failure, with particular focus on the role of ADMA and DDAH1.

Keywords: Asymmetric dimethylarginine; Dimethylarginine dimethylaminohydrolase-1; Heart failure; Nitric oxide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amidohydrolases / genetics
  • Amidohydrolases / metabolism
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Heart Failure / etiology
  • Heart Failure / metabolism*
  • Humans
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Peroxynitrous Acid / metabolism
  • Signal Transduction
  • Superoxides / metabolism
  • omega-N-Methylarginine / metabolism

Substances

  • Superoxides
  • Peroxynitrous Acid
  • omega-N-Methylarginine
  • Nitric Oxide
  • N,N-dimethylarginine
  • Arginine
  • Nitric Oxide Synthase
  • Amidohydrolases
  • dimethylargininase